Cholesterol lowering eye drops `may fight sight loss`

New Delhi: A new study led by an Indian origin scientist suggests that eye drops designed to lower cholesterol may be able to save sight in some people with a common cause of age-related vision loss.

The study, which was supported by the National Institutes of Health, showed that large cells called macrophages appear to play a key role in clearing cholesterol from the eye, and that with aging, these cells become less efficient at this task.

Eye drops containing a type of drug known to promote cholesterol release from macrophages, called a liver X receptor (LXR) agonist, helped restore macrophage function and prevent AMD progression in a mouse model.

The study was led by Rajendra Apte, M.D., Ph.D., a professor of ophthalmology and vision sciences at Washington University in St. Louis.

AMD causes damage to the macula, a region of the retina responsible for central, high-resolution vision. The macula is dense with light-sensing cells called photoreceptors, and is what humans rely on for tasks that require sharp vision, such as reading, driving, and recognizing faces.

This sharp vision deteriorates in AMD, which can take two forms. In one, sometimes referred to as dry AMD, vision loss is due to a gradual loss of photoreceptors in the macula. In the other, referred to as wet or neovascular AMD, abnormal blood vessels grow under the macula, leaking blood and causing rapid damage to the photoreceptors.

"This study points to a novel strategy for early intervention to prevent the progression of AMD to the severe neovascular form of the disease," said Grace Shen, Ph.D., a program director at NIH`s National Eye Institute, which funded the research.

In previous studies, Dr. Apte found that macrophages normally help limit the growth of new blood vessels in the eye, but with age, the cells lose this ability. The new study suggests that prior to these changes, old macrophages become less efficient at processing cholesterol.

A protein called ABCA1 is needed for macrophages to release cholesterol into the bloodstream. In these experiments on mice, Dr. Apte and his team found that in old macrophages, there is a decrease in the level of ABCA1 protein. The researchers found a similar drop in ABCA1 levels in blood cells-the source of macrophages-in samples donated by older people (ages 67-87) vs. younger ones (ages 25-34). The ABCA1 gene has been identified as a risk factor for AMD.

To investigate the link between these changes and blood vessel growth, the researchers first performed tests in cell culture. When grown in a dish with blood vessel cells, young macrophages efficiently stopped the cells from multiplying, but old macrophages did not. Deleting the ABCA1 gene in young macrophages caused them to behave like old macrophages.

Next, the researchers tried treating old macrophages with an LXR agonist; these drugs are known to enhance cholesterol transport from macrophages by turning on the ABCA1 gene. Exposure to the drug rejuvenated the old macrophages and enabled them to inhibit blood vessel cell growth.

The researchers also tested the LXR agonist in mice with an eye injury that produces abnormal blood vessel growth, similar to that seen in neovascular AMD. Eye drops of the drug significantly reduced this blood vessel growth when given several days before the injury.